Arsenic-induced toxicity: effect on protein composition in sciatic nerve

2006 ◽  
Vol 25 (11) ◽  
pp. 667-674 ◽  
Author(s):  
A Vahidnia ◽  
F Romijn ◽  
M Tiller ◽  
G B van der Voet ◽  
F A de Wolff
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Protein Composition ◽  
Arsenic Compounds ◽  
Neurotoxic Effects ◽  
Electrophysiological Studies ◽  
Male Wistar Rats ◽  
Sciatic Nerves ◽  
L Proteins

Exposure to arsenic compounds may lead to skin and lung cancer and various disorders such as vascular disease and peripheral neuropathy in humans. Peripheral arsenic neurotoxicity has been demonstrated clinically and in electrophysiological studies. Patients intoxicated with arsenic show neurological symptoms in their feet and hands. These patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison with controls. The mechanism of arsenic peripheral nervous system (PNS) toxicity, however, has never been described before. This is the first study to investigate the toxicity of arsenic on the PNS. Male Wistar rats were exposed to arsenite given as a single dose i.v. After sacrifice, sciatic nerves were excised and the protein composition was analysed. Protein analysis of sciatic nerves showed disappearance of neurofilament and fibroblast proteins in rats treated with arsenite doses of 15 and 20 mg/kg in comparison with the control groups. Some fibroblast protein bands had disappeared in the 20-mg/kg dose group. The analysed neurofilament-M and-L proteins decreased dose dependency over time. arsenic affects the composition of proteins in the rat sciatic nerve, especially the neurofilaments. The reduction of signals in Western blot analysis reveals changes in cytoskeletal composition, which may well lead to neurotoxic effects in vivo.

Prevention of painful neuromas by oblique transection of peripheral nerves

2006 ◽  
Vol 104 (2) ◽  
pp. 285-289 ◽  
Author(s):  
Wieslaw Marcol ◽  
Katarzyna Kotulska ◽  
Magdalena Larysz-Brysz ◽  
Grazyna Bierzyñska-Macyszyn ◽  
Pawel Wlaszczuk ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Traditional Method ◽  
Healing Process ◽  
Nerve Transection ◽  
Proximal Stump ◽  
Sciatic Nerves ◽  
Neuroma Formation

Object Neuroma formation often occurs at the proximal stump of the transected nerve, complicating the healing process after gap injuries or nerve biopsies. Most such neuromas cause therapy-resistant neuropathic pain. The purpose of this study was to determine whether oblique transection of the proximal stump of the sciatic nerve can prevent neuroma formation. Methods The sciatic nerves of 10 rats were transected unilaterally at an angle of 30°, and the peripheral segments of the nerves were removed. In 10 control animals the sciatic nerves were transected at a perpendicular angle. Twenty weeks after surgery the nerves were reexposed and collected. The presence of neuromas was determined by two board-certified pathologists on the basis of histopathological evaluations. Conclusions The oblique transection of peripheral nerves, contrary to perpendicularly transected nerves, is rarely followed by classic neuroma development. Moreover, neuropathic pain is significantly reduced compared with that following the traditional method of nerve transection.

Chronic effects of muscle and nerve-directed stretching on tissue mechanics

2020 ◽  
Vol 129 (5) ◽  
pp. 1011-1023 ◽  
Author(s):  
Ricardo J. Andrade ◽  
Sandro R. Freitas ◽  
François Hug ◽  
Guillaume Le Sant ◽  
Lilian Lacourpaille ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Tissue Mechanics ◽  
Plantar Flexor ◽  
Chronic Effects ◽  
Flexor Muscles ◽  
Plantar Flexor Muscles

This study demonstrates that the mechanical properties of plantar flexor muscles and sciatic nerve can adapt mechanically to long-term stretching programs. Although interventions targeting muscular or nonmuscular structures are both effective at increasing maximal range of motion, the changes in tissue mechanical properties (stiffness) are specific to the structure being preferentially stretched by each program. We provide the first in vivo evidence that stiffness of peripheral nerves adapts to long-term loading stimuli using appropriate nerve-directed stretching.

scholarly journals Tumors Provoke Inflammation and Perineural Microlesions at Adjacent Peripheral Nerves

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 320 ◽  
Author(s):  
Jennifer Cohnen ◽  
Lisa Kornstädt ◽  
Lisa Hahnefeld ◽  
Nerea Ferreiros ◽  
Sandra Pierre ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Neuronal Damage ◽  
Physical Contact ◽  
Melanoma Tumor ◽  
Inflammatory Processes ◽  
Sciatic Nerves ◽  
Tumor Types ◽  
Junction Proteins ◽  
Time Point

Cancer-induced pain occurs frequently in patients when tumors or their metastases grow in the proximity of nerves. Although this cancer-induced pain states poses an important therapeutical problem, the underlying pathomechanisms are not understood. Here, we implanted adenocarcinoma, fibrosarcoma and melanoma tumor cells in proximity of the sciatic nerve. All three tumor types caused mechanical hypersensitivity, thermal hyposensitivity and neuronal damage. Surprisingly the onset of the hypersensitivity was independent of physical contact of the nerve with the tumors and did not depend on infiltration of cancer cells in the sciatic nerve. However, macrophages and dendritic cells appeared on the outside of the sciatic nerves with the onset of the hypersensitivity. At the same time point downregulation of perineural tight junction proteins was observed, which was later followed by the appearance of microlesions. Fitting to the changes in the epi-/perineurium, a dramatic decrease of triglycerides and acylcarnitines in the sciatic nerves as well as an altered localization and appearance of epineural adipocytes was seen. In summary, the data show an inflammation at the sciatic nerves as well as an increased perineural and epineural permeability. Thus, interventions aiming to suppress inflammatory processes at the sciatic nerve or preserving peri- and epineural integrity may present new approaches for the treatment of tumor-induced pain.

Waterjet Dissection of Peripheral Nerves: An Experimental Study of the Sciatic Nerve of Rats

2010 ◽  
Vol 67 (suppl_2) ◽  
pp. ons368-ons376 ◽  
Author(s):  
Christoph A. Tschan ◽  
Doerthe Keiner ◽  
Harald D. Müller ◽  
Kerstin Schwabe ◽  
Michael R. Gaab ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Peripheral Nerves ◽  
Scar Tissue ◽  
Small Water ◽  
Peripheral Nerve Surgery ◽  
Sciatic Nerves ◽  
Nerve Surgery ◽  
Waterjet Dissection

ABSTRACT BACKGROUND: Although waterjet dissection has been well evaluated in intracranial pathologies, little is known of its qualities in peripheral nerve surgery. Theoretically, the precise dissection qualities could support the separation of nerves from adjacent tissues and improve the preservation of nerve integrity in peripheral nerve surgery. OBJECTIVE: To evaluate the potential of the new waterjet dissector in peripheral nerve surgery. METHODS: Waterjet dissection with pressures of 20 to 80 bar was applied on the sciatic nerves of 101 rats. The effect of waterjet dissection on the sciatic nerve was evaluated by clinical tests, neurophysiological examinations, and histopathological studies up to 12 weeks after surgery. RESULTS: With waterjet pressures up to 30 bar, the sciatic nerve was preserved in its integrity in all cases. Functional damaging was observed at pressures of 40 bar and higher. However, all but 1 rat in the 80 bar subgroup showed complete functional regeneration at 12 weeks after surgery. Histopathologically, small water bubbles were observed around the nerves. At 40 bar and higher, the sciatic nerves showed signs of direct nerve injury. However, all these animals showed nerve regeneration after 12 weeks, as demonstrated by histological studies. CONCLUSION: Sciatic nerves were preserved functionally and morphologically at pressures up to 30 bar. Between 40 and 80 bar, reliable functional and morphological nerve regeneration occurred. Waterjet pressures up to 30 bar might be applied safely under clinical conditions. This technique might be well suited to separate intact peripheral nerves from adjacent tumor or scar tissue. Further studies will have to show the clinical relevance of these dissection qualities.

scholarly journals Interfacial polarization of in vivo rat sciatic nerve with crush injury studied via broadband dielectric spectroscopy

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252589
Author(s):  
Risa Otagiri ◽  
Hideki Kawai ◽  
Masanobu Takatsuka ◽  
Naoki Shinyashiki ◽  
Akira Ito ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Dielectric Spectroscopy ◽  
Peripheral Nerves ◽  
Room Temperature ◽  
Cell Structure ◽  
Interfacial Polarization ◽  
Broadband Dielectric Spectroscopy ◽  
Sciatic Nerves ◽  
The Difference

Electrical stimulation is one of the candidates for elongation-driven regeneration of damaged peripheral nerves. Different organs and tissues have an inherent cell structure and size. This leads to variation in the tissue-specific electrical properties of the frequency of interfacial polarization. Although nervous tissues have a membrane potential, the electrical reaction inside these tissues following electrical stimulation from outside remains unexplored. Furthermore, the pathophysiological reaction of an injured nerve is unclear. Here, we investigated the electrical reaction of injured and non-injured rat sciatic nerves via broadband dielectric spectroscopy. Crush injured and non-injured sciatic nerves of six 12-week-old male Lewis rats were used, 6 days after infliction of the injury. Both sides of the nerves (with and without injury) were exposed, and impedance measurements were performed at room temperature (approximately 25°C) at frequencies ranging from 100 mHz to 5.5 MHz and electric potential ranging from 0.100 to 1.00 V. The measured interfacial polarization potentially originated from the polarization by ion transport around nerve membranes at frequencies between 3.2 kHz and 1.6 MHz. The polarization strength of the injured nerves was smaller than that of non-injured nerves. However, the difference in polarization between injured and non-injured nerves might be caused by inflammation and edema. The suitable frequency range of the interfacial polarization can be expected to be critical for electrical stimulation of injured peripheral nerves.

scholarly journals Proteins from sciatic-nerve myelin in quaking and jimpy mice

1978 ◽  
Vol 173 (3) ◽  
pp. 989-991 ◽  
Author(s):  
J M Matthieu
Keyword(s):  
Sciatic Nerve ◽  
Protein Composition ◽  
Myelin Proteins ◽  
Myelin Protein ◽  
Sciatic Nerves ◽  
Jimpy Mice ◽  
Quaking Mice

Myelin from two neurological mutants in mice was isolated from sciatic nerves and its protein composition analysed. In Quaking mice, two intrinsic myelin proteins P1 and P2 were drastically decreased, whereas the major myelin protein P0 was unaffected. A normal protein composition was found in sciatic myelin from Jimpy mice.

scholarly journals EXPERIMENTAL STUDY OF THE NEUROTOXIC EFFECTS OF PHOTODYNAMIC THERAPY ON THE SPINAL CORD

2019 ◽  
Vol 18 (3) ◽  
pp. 176-180
Author(s):  
HERTON RODRIGO TAVARES COSTA ◽  
ELAINE APARECIDA DEL BEL BELLUZ GUIMARÃES ◽  
ANTÔNIO CLAUDIO TEDESCO ◽  
FERNANDO LUCAS PRIMO ◽  
CÉLIA APARECIDA DA SILVA ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Photodynamic Therapy ◽  
Dura Mater ◽  
Aluminum Chloride ◽  
Control Group ◽  
Functional Evaluation ◽  
Neurotoxic Effects ◽  
Pathological Evaluation ◽  
Male Wistar Rats

ABSTRACT Objective To evaluate the effects of photodynamic therapy (PDT) on the dura mater using the photosensitizers aluminum chloride phthalocyanine and methylene blue in in vivo assays. Methods Fifty-six male Wistar rats were divided into two groups; one submitted to PDT and the other submitted to the photosensitizers without their photoactivation (control). The photosensitizers were applied to the dura mater after laminectomy at the T10 level. The methods used for assessment were the Basso, Beattie and Bresnahan (BBB) functional evaluation scale and study of the dura mater by light microscopy. Results No changes in motor activity were observed in the animals submitted to PDT compared to control. Histological and pathological evaluation did not show any differences between the group exposed to activated photosensitizers and the control group with regard to the inflammatory process and tissue necrosis. Conclusion The joint use of PDT with the photosensitizing pharmaceuticals aluminum chloride phthalocyanine and methylene blue did not induce any clinical neurotoxic effects or histological changes in the dura mater of the animals studied. Level de evidence V; Expert Opnion.

scholarly journals MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study

2020 ◽  
Vol 7 ◽  
Author(s):  
Vlad Tereshenko ◽  
Irena Pashkunova-Martic ◽  
Krisztina Manzano-Szalai ◽  
Joachim Friske ◽  
Konstantin D. Bergmeister ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Peripheral Nerves ◽  
Proof Of Concept ◽  
Peripheral Nerve Injuries ◽  
Radiological Imaging ◽  
Nerve Injuries ◽  
Experimental Proof

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

Biocompatibility of Hylan Polymers in Various Tissue Compartments

1995 ◽  
Vol 394 ◽  
Author(s):  
N.E. Larsen ◽  
E. Leshchiner ◽  
E.A. Balazs ◽  
C. Belmonte
Keyword(s):  
Adverse Effect ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Tissue Reaction ◽  
Tissue Response ◽  
Medical Applications ◽  
Biological Compatibility ◽  
Sciatic Nerves ◽  
Tissue Compartments

AbstractHylans (hyaluronan derivatives) retain the biological compatibility of the natural hyaluronan and have enhanced rheological properties which expands their utility in medical applications. Hylan materials (hylan A fluid, hylan B gel) were evaluated in a variety of tissue compartments for local and systemic tissue reaction (gross and microscopic), residence time and overall behavior in vivo. Hylan material was implanted into the subcutaneous, intradermal, submucosal, intramuscular, eye (vitreus, anterior chamber, trabecular meshwork), and neural (sciatic nerve) tissues at volumes ranging from 0.50 ml/kg to 20 ml/kg (2.5 mg/kg to 100 mg/kg). There was no difference in tissue response to hylan implants at the various ‘doses’ evaluated; all samples tested were observed to be biocompatible and did not elicit significant tissue response. Therefore, tissue reaction of hylan implants was not dependent on dose or concentration of hylan administered, since implantation of small amounts resulted in the same response as implantation of large amounts of material. In one of the most sensitive tests of biocompatibility, hylan was found to have no adverse effect on nerve regeneration (severed sciatic nerves in rat), and the results indicated that hylan materials “regeneration-friendly” environment for peripheral nerve growth as commatpearriaelds tpor othveid BedS Sa controls.Hylan materials provide biologically and physically compatible intercellular matrices which are useful in a variety of medical applications, including use as viscosurgical and viscoprotective tools (to maintain space, separate and protect tissues) and as viscosupplementation devices and implants.

Prolonged Regional Nerve Blockade

1996 ◽  
Vol 84 (6) ◽  
pp. 1401-1410 ◽  
Author(s):  
Joanne Curley ◽  
Jenny Castillo ◽  
Joyce Hotz ◽  
Megumi Uezono ◽  
Sonia Hernandez ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerves ◽  
Glycolic Acid ◽  
Scintillation Counting ◽  
Biodegradable Microspheres ◽  
Solvent Evaporation Method ◽  
Significant Prolongation ◽  
Surgical Implantation

Background Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats. Methods Microspheres were prepared using polylactic-co-glycolic acid polymers loaded with 75% w/w bupivacaine by a solvent evaporation method. Bupivacaine release from microspheres was determined in vitro by ultraviolet spectroscopy and scintillation counting. Sensory and motor blockade of the rat sciatic nerve were assessed in vivo after injection of microsphere suspensions. Results Depending on the type of microspheres, the dose, and the additive used, mean duration of sciatic nerve block ranged from 10 h to 5.5 days. Incorporation of 0.05% w/w dexamethasone into the microspheres resulted in significant prolongation of block (up to 13-fold), and only preparations that contained dexamethasone produced blocks lasting beyond 1 day. Bupivacaine was released in a controlled manner in vitro. Dexamethasone does not substantially slow bupivacaine release from microspheres in vitro. Conclusions Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.

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